KCNB1基因变异相关发育性癫痫性脑病的临床特点分析

Clinical features of KCNB1 gene variation related developmental and epileptic encephalopathy

目的总结KCNB1基因变异相关癫痫和(或)发育落后患儿的临床特点。方法病例系列研究,选取2015年7月至2024年6月在北京大学第一医院儿童医学中心和深圳市儿童医院神经内科诊治的24例KCNB1基因变异相关癫痫和(或)发育落后的患儿,对患儿的癫痫发作表现、脑电图和基因检测结果等进行分析。结果24例患儿KCNB1基因变异均为新生变异,包括20个不同的变异位点,其中错义变异15个、移码变异3个、无义变异2个,7个变异尚未见报道。24例发育性癫痫性脑病患儿中男14例、女10例,末次随访年龄9月龄至13岁9月龄。21例(88%)患儿有癫痫发作,癫痫起病年龄为1月龄至7岁,其中76%(16/21)在2岁前发病。癫痫发作类型包括局灶性发作15例(71%),癫痫性痉挛发作、肌阵挛发作和全面强直阵挛发作各6例,不典型失神发作4例,肌阵挛失张力发作1例,17例(81%)发作有丛集性特点。5例有局灶性发作伴意识障碍持续状态史。24例患儿均有不同程度发育落后,其中3例仅表现为发育落后。21例有癫痫发作的患儿脑电图均存在异常,其中发作间期局灶性或多灶性放电20例,广泛性放电10例,高峰失律2例,睡眠中癫痫性电持续状态3例。24例患儿中,5例颅脑磁共振成像显示有异常。21例有癫痫发作的患儿中,12例(57%)发作已控制。结论KCNB1基因变异以新生错义变异为主,多数患儿有癫痫发作,少数可仅表现为发育落后。癫痫多数在2岁前起病,以局灶性发作最常见,约80%的患儿发作有丛集性特点。虽然多数患儿癫痫发作可控制,但仍有不同程度的发育落后,符合发育性癫痫性脑病的特点。

ObjectiveTo summarize the clinical features of epilepsy and(or)developmental delay associated with KCNB1 gene variants in children.MethodsA case series study was conducted on 24 children with KCNB1 gene variants associated with epilepsy and(or)developmental delay who were treated at the Children′s Medical Center of Peking University First Hospital and the Department of Neurology of Shenzhen Children′s Hospital from July 2015 to June 2024.The manifestations of seizures,electroencephalogram(EEG)and genetic test results of those children were analyzed.ResultsAll the KCNB1 gene variants were de novo,involving 20 different variation,including 15 missense variations,3 frameshift variations and 2 nonsense variations.There were 7 novel variations.Among the 24 developmental and epileptic encephalopathy children,there were 14 boys and 10 girls.The last follow-up age ranged from 9 months to 13 years and 9 months.Seizures were present in 21 children(88%),with onset ranging from 1 month to 7 years,and 76%(16/21)began before 2 years of age.The seizure types included focal seizures in 15 children(71%),epileptic spasms,myoclonic seizures,and generalized tonic-clonic seizures in 6 children respectively,atypical absence seizures in 4 children,and myoclonic atonic seizures in 1 child.Seventeen children(81%)had a cluster of seizures and 5 had a history of focal status epilepticus with impaired consciousness.All 24 children had varying degrees of developmental delay,with 3 presenting solely developmental delay.EEG abnormalities were present in all the 21 children with seizures,including focal or multifocal discharges in 20 children,generalized discharges in 10 children,hypsarrhythmia in 2 children,and electrical status epilepticus during sleep in 3 children.Magnetic resonance imaging abnormalities were found in 5 of the 24 children.Among the 21 children with seizures,57%(12/21)achieved seizure control.ConclusionsKCNB1 gene variants are predominantly de novo missense variation.Most affected children present with epilepsy,though some may exhibit only developmental delay.Epilepsy often begins before 2 years of age,with focal seizures being the most common type.About 80%of patients experience clustered seizures.Although most patients achieve seizure control,they still exhibit varying degrees of developmental delay,consistent with developmental epileptic encephalopathy.